title: Repressed synthesis of ribosomal proteins generates protein-specific cell cycle and morphological phenotypes.
abstract: The biogenesis of ribosomes is coordinated with cell growth and proliferation. Distortion of the coordinated synthesis of ribosomal components affects not only ribosome formation, but also cell fate. However, the connection between ribosome biogenesis and cell fate is not well understood. To establish a model system for inquiries into these processes, we systematically analyzed cell cycle progression, cell morphology, and bud site selection after repression of 54 individual ribosomal protein (r-protein) genes in Saccharomyces cerevisiae. We found that repression of nine 60S r-protein genes results in arrest in the G2/M phase, whereas repression of nine other 60S and 22 40S r-protein genes causes arrest in the G1 phase. Furthermore, bud morphology changes after repression of some r-protein genes. For example, very elongated buds form after repression of seven 60S r-protein genes. These genes overlap with, but are not identical to, those causing the G2/M cell cycle phenotype. Finally, repression of most r-protein genes results in changed sites of bud formation. Strikingly, the r-proteins whose repression generates similar effects on cell cycle progression cluster in the ribosome physical structure, suggesting that different topological areas of the precursor and/or mature ribosome are mechanistically connected to separate aspects of the cell cycle.
authors.affiliation: Department of Biological Sciences, University of Maryland, Baltimore County, Baltimore, MD 21250 Flow Cytometry Core Facility, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Mamata
authors.initials: M
authors.lastname: Thapa
authors.forename: Ananth
authors.initials: A
authors.lastname: Bommakanti
authors.forename: Md
authors.initials: M
authors.lastname: Shamsuzzaman
authors.forename: Brian
authors.initials: B
authors.lastname: Gregory
authors.forename: Leigh
authors.initials: L
authors.lastname: Samsel
authors.forename: Janice M
authors.initials: JM
authors.lastname: Zengel
authors.forename: Lasse
authors.initials: L
authors.lastname: Lindahl
mesh_terms: D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D004271:DNA, Fungal / Q000378:metabolism; D005434:Flow Cytometry; D008954:Models, Biological; D010641:Phenotype; D014176:Protein Biosynthesis; D012269:Ribosomal Proteins / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: D004271:DNA, Fungal; D012269:Ribosomal Proteins; D029701:Saccharomyces cerevisiae Proteins